What orthopaedic surgeons should do when notified of an allograft tissue recall or market withdrawal

The March/April 2007 issue of AAOS Now addressed the critical role orthopaedic surgeons play in ensuring the public health through the reporting of adverse events (“MedWatch: Your link to adverse event reporting”). This issue examines the actions orthopaedic surgeons should take when notified of a tissue recall or market withdrawal.

For several decades, orthopaedic surgeons have routinely used allograft tissue for skeletal reconstruction. It is estimated that more than 1 million individual grafts will be implanted in patients in the United States in 2007. Although the industry record for safety has been quite good, tissue recalls and market withdrawals do happen, and user physicians must know how to respond to these recalls to ensure optimal care of their patients.

Voluntary and FDA-mandated recalls
Tissue recalls may be voluntary or mandated by the U.S. Food and Drug Administration (FDA). Voluntary market withdrawals can occur and are facilitated by the tissue processor. The FDA has the authority to order a recall if they deem the tissue to pose a hazard to public health.

Recalls fall into three classifications

• Class I recall – There is reasonable probability that use or exposure will cause a serious adverse health consequences or death. FDA-mandated recalls generally fit into this classification.
• Class II recall – This recall pertains to use or exposure that may cause temporary or medically reversible adverse health consequences or to situations in which the probability of serious adverse health consequences is remote. A number of voluntary recalls instituted by manufacturers are eventually categorized by the FDA as either Class I or Class II mandated recalls.
• Class III recall – This represents less risk than a Class II recall. Although there is only a slight risk of a health problem in this type of recall, the product may have violated some part of federal law.

Between 1993 and 2005, approximately 18,000 individual tissue products were recalled (including skin, heart valves, corneas, and musculoskeletal tissues). The Biomedical Tissue Services recall during the last quarter of 2005 alone created a recall of approximately 25,000 pieces of tissue. To date, none of the tissues recovered by Biomedical Tissue Service have been verified as a source of any proven associated allograft-caused infections.

Why recalls are issued
The FDA adverse reactions reporting system for human cells, tissues, and cellular and tissue-based products (HCT/Ps) states that manufacturers must investigate any adverse reactions involving a communicable disease related to an HCT/P that they made available for distribution. Manufacturers must report to the FDA any adverse reaction involving a communicable disease if it is:

• Fatal
• Life-threatening
• Results in permanent impairment of function or permanent damage to the body structure, or
• Requires medical or surgical intervention including hospitalization.

An adverse reaction is defined as an unintended response to any HCT/P for which there is a reasonable probability that the HCT/P caused the response. Adverse reactions should be reported within 15 days of receipt of information, using form FDA 3500A (for mandatory reporting by manufacturers) and form FDA 3500 (for voluntary reporting by healthcare professionals). An adverse reaction also necessitates prompt reporting directly to the HCT/P tissue establishment that produced the HCT/P.

Manufacturers are also required to report HCT/P deviations. The deviation may be an error such as an event that deviates from applicable regulations, standards, or established specifications relating to the prevention of disease transmission or contamination. In addition, manufacturers must report any accident—such as an unexpected unforeseeable event that may be related to transmission or potential transmission of communicable disease, or may lead to HCT/P contamination—to the FDA. This is accomplished using form FDA-3486 as soon as possible, not to exceed 45 days after discovery.

What should an orthopaedist do when notified of a recall?
When orthopaedic surgeons are notified of a quarantine or recall, the first step should be to contact their institution’s hospital tissue storage bank, tissue bank and supplier facility or, if neither of the other entities exists, the institution’s infectious disease control committee. The tissue supplier should be contacted as well. The orthopaedist should also seek specific, written details about the recall from the FDA and the Centers for Disease Control and Prevention (CDC) as soon as possible. Orthopaedic surgeons should be active participants in clarifying whether this recall directly impacts their own orthopaedic clinical practices.

When a recall occurs, hospital or facility representatives will identify the status of the recalled tissue and should immediately quarantine any unused tissue at the institution and then expedite its return to the manufacturer. Tissues should be identified as soon as possible using tissue tracking methods at the institution, and surgeons should be notified of the status (ie, still in inventory, transplanted, or disposed of).

Mandatory recall = Serious risk to public health
Surgeons should understand that a mandatory recall is only issued when the FDA believes there is a serious risk to public health. Recalls may focus on processing techniques at a specific facility, which may affect many tissues. The musculoskeletal tissue bank or distributor, in conjunction with the FDA and CDC, will provide recommendations regarding whether recipients of recalled tissues should be contacted by the surgeon or by the hospital/facility. Identifying, locating, and then contacting affected recipients should be performed without delay.

A coordinated approach
Facilities may want to consider a coordinated approach to communicating with patients when a major recall occurs. For example, one surgeon may be designated to contact all of the affected patients to ensure that the message is delivered in a consistent manner. Later, the implanting surgeon may schedule time to discuss the patient’s concerns and questions regarding disease transmission, costs of recommended testing, and other aspects of their care.

All recalled tissues must be tracked to confirm their locations—whether they are in the facility’s inventory, discarded, or implanted. If the FDA and CDC declare that the specific incident posed minimal risk to patients and indeed was a voluntary recall, it may not be necessary for any action to be taken on tissue that was already implanted. However, the FDA and CDC may recommend infectious disease testing for patients implanted with tissue from a mandated recall. Because the serologic tests for living donors have narrow false-negative window periods for detecting viruses using nucleic acid testing methods, repetitive serologic surveillance over many months should not be required. CDC recommendations may be accessed at http://www.cdc.gov/tTFAQ.html.

Millions of allografts have been implanted over the last 20 years with only a few confirmed viral or bacterial infection transmissions, making allografts a safe option for skeletal reconstruction. The AAOS urges all fellows to follow rigorous federal regulations and guidelines, and recommends the use of tissue from banks accredited by the American Association of Tissue Banks (AATB).

Michael J. Joyce, MD, is a member of the Biological Implants Committee and advises the fellowship and committee on tissue banking matters. A past president of AATB, Dr. Joyce specializes in tumor surgery at the Cleveland Clinic. He can be reached at joycem@ccf.org.

Resources
US Code of Federal Regulations 21 CFR Part 1271,
www.accessdata.fda.gov/.cfm

US Food and Drug Administration, MedWatch,
www.fda.gov/MedWatch.

American Association of Tissue Banks,
www.aatb.org

Guidance for the Industry: Eligibility Determination for Donors of Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps),
www.fda.gov/cber/guidelines.htm